Synaptic transmission : ion concentration changes in the synaptic cleft

1979 ◽  
Vol 206 (1162) ◽  
pp. 115-131 ◽  
Keyword(s):  
Neuromuscular Junction ◽  
Time Course ◽  
Reversal Potential ◽  
Synaptic Cleft ◽  
Time Dependent ◽  
Ion Concentration ◽  
Frog Neuromuscular Junction ◽  
Synaptic Current ◽  
Sodium Depletion ◽  
Concentration Changes

Currents flowing through the postsynaptic membrane of an active synapse will tend to change the concentrations of ions in the synaptic cleft. Published experimental data are used to predict ( a ) the sodium and potassium concentration changes in the cleft at the frog neuromuscular junction, and ( b ) the sodium depletion in the cleft under a Ia synaptic bouton on a cat motoneuron. Significant concentration changes are predicted at both synapses. These changes will contribute to the time dependence of the observed current and will cause the reversal potential of the current to be time dependent. At the frog neuromuscular junction, the time course of the endplate current has been shown previously to depend on the magnitude of the current flowing (at a given potential). We attribute this to changes of the cleft ion concentration. The time dependent changes of the endplate current reversal potential that we predict for the neuromuscular junction are probably too small to be detected. This is because the effects of sodium depletion and potassium accumulation on the reversal potential almost cancel. We predict that near the reversal potential small currents of complex time course will remain, i. e. no true reversal potential exists. Such currents have previously been seen experimentally. At the cat Ia synapse, the synaptic current is predicted to deplete a significant fraction of the available extracellular sodium ions. Consequently, the magnitude of the synaptic current should be relatively independent of the number of postsynaptic channels activated, and of the membrane potential, as has previously been found experimentally.

Prolonged Physiological Entrapment of Glutamate in the Synaptic Cleft of Cerebellar Unipolar Brush Cells

1997 ◽  
Vol 78 (3) ◽  
pp. 1320-1333 ◽  
Author(s):  
Gregory A. Kinney ◽  
Linda S. Overstreet ◽  
N. Traverse Slater
Keyword(s):  
Steady State ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Time Course ◽  
Synaptic Cleft ◽  
Synaptic Current ◽  
Brush Cells ◽  
Glutamate Concentration ◽  
Steady State Current ◽  
Unipolar Brush Cells

Kinney, Gregory A., Linda S. Overstreet, and N. Traverse Slater. Prolonged physiological entrapment of glutamate in the synaptic cleft of cerebellar unipolar brush cells. J. Neurophysiol. 78: 1320–1333, 1997. The cellular mechanism underlying the genesis of the long-lasting α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor-mediated excitatory postsynaptic currents (EPSCs) at the mossy fiber (MF)–unipolar brush cell (UBC) synapse in rat vestibular cerebellum was examined with the use of whole cell and excised patch-clamp recording methods in thin cerebellar slices. Activation of MFs evokes an all-or-none biphasic AMPA-receptor-mediated synaptic current with a late component that peaks at 100–800 ms, which has been proposed to originate from an entrapment of glutamate in the MF-UBC synaptic cleft and is generated by the steady-state activation of AMPA receptors. Bath application of cyclothiazide, which blocks desensitization of AMPA receptors, produced a dose-dependent enhancement of the amplitude of the synaptic current (median effective dose 30 μM) and slowing of the rise time of the fast EPSC. N-methyl-d-aspartate-receptor-mediated EPSCs in UBCs were not potentiated in amplitude or time course by cyclothiazide (100 μM). The dose-response relations for the steady-state current evoked by glutamate acting at AMPA receptors in excised outside-out patches from UBC and granule somatic membranes was biphasic, peaking at 50 μM and declining to 50–70% of this value at 1 mM glutamate. When glutamate was slowly washed from patches to simulate the gradual decline of glutamate in the synapse, a late hump in the transmembrane current was observed in patches from both cell types. The delivery of a second MF stimulus at the peak of the slow EPSC evoked a fast EPSC of reduced amplitude followed by an undershoot of the subsequent slow current, consistent with the hypothesis that the peak of the slow EPSC reflects the peak of the biphasic steady-state dose-response curve. Estimates of receptor occupancy and glutamate concentration derived from the ratio of fast EPSC amplitudes, and the amplitude and polarity of the initial steady-state current in paired-pulse experiments, predict a slow decline of glutamate with a time constant of 800 ms, declining to ineffective concentrations at 5.4 s. Manipulation of cleft glutamate concentration by lowered extracellular calcium or delivery of brief stimulus trains abolished the slow EPSC and restored the undershoot to paired stimuli, respectively, in a manner consistent with a prolonged lifetime of glutamate in the cleft. The slow component of the EPSC was prolonged in duration by the glutamate reuptake inhibitor l- trans-pyrrolidine-2,4-dicarboxylate, suggesting that glutamate transport contributes to the time course of the synaptic current in UBCs. The data support the notion that the MF-UBC synapse represents an ultrastructural specialization to effectively entrap glutamate for unusually prolonged periods of time following release from MF terminals. The properties of the postsynaptic receptors and constraints on diffusional escape of glutamate imposed by synaptic ultrastructure and glutamate transporters act in concert to sculpt the time course of the resulting slow EPSC. This in turn drives a long-lasting train of action potentials in response to single presynaptic stimuli.

Basolateral membrane Cl- and K+ conductances of the dark-adapted chick retinal pigment epithelium

1993 ◽  
Vol 70 (4) ◽  
pp. 1656-1668 ◽  
Author(s):  
R. P. Gallemore ◽  
E. Hernandez ◽  
R. Tayyanipour ◽  
S. Fujii ◽  
R. H. Steinberg
Keyword(s):  
Retinal Pigment Epithelium ◽  
Time Course ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Basolateral Membrane ◽  
Basal Membrane ◽  
Diffusion Potential ◽  
Ion Concentration ◽  
Concentration Changes ◽  
Cl Conductance

1. We characterized the basolateral membrane Cl- and K+ conductances of the dark-adapted chick neural retina-retinal pigment epithelium (RPE)-choroid preparation. Conventional microelectrodes were used to measure apical (V(ap)) and basolateral (Vba) membrane voltage, and double-barreled Cl- and K+ selective microelectrodes were used to follow the time course and magnitude of ion concentration changes outside the basolateral (basal) membrane. 2. In response to a fivefold decrease in basal [Cl-]o, Vba rapidly depolarized by 6.4 +/- 0.7 (SE) mV, and the apparent resistance of the basolateral membrane (Rba) increased. The Cl- channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) suppressed the Vba depolarization by 40% and blocked the Rba increase. Estimates of the relative Cl- conductance (transference number, TCl) from the DIDS-sensitive component of the Cl- diffusion potential gave an average value for TCl of 0.22 +/- 0.03. 3. Further evidence for a Cl- conductance was obtained by measuring changes in intracellular Cl- activity (aCli) induced by transtissue current. Depolarizing Vba elevated aiCl, whereas hyperpolarizing Vba had the opposite effect, consistent with conductive Cl- movement across the basal membrane. TCl estimated from these data averaged 0.23 +/- 0.02. 4. In response to a sixfold increase in basal [K+]o, Vba depolarized 6.1 +/- 0.8 mV. The amplitude of this K+ diffusion potential was inhibited 44 and 67% by 5 and 10 mM Ba2+, respectively. TK was estimated to be 0.61 +/- 0.05. 5. The rapid c-wave membrane hyperpolarizations in response to the light-evoked decrease in subretinal [K+]o were used to calculate the equivalent resistances of the apical membrane (R(ap)), basolateral membrane (Rba), and the paracellular shunt pathway (Rs). They were 152 +/- 10, 615 +/- 38, and 138 +/- 7 omega.cm2 (n = 11 tissues), respectively. From these data the equivalent electromotive force for the basal (Eba) and apical (Eap) membranes were estimated to be -45 +/- 2 and -77 +/- 1 mV, respectively. This estimate of Eba is in the range of that predicted from our estimates of TCl and TK, indicating that, in the dark-adapted chick retina, the resting conductance of the basal membrane can largely be accounted for by the Cl- and K+ conductances described here.

scholarly journals Desensitization and recovery at the frog neuromuscular junction.

1977 ◽  
Vol 69 (4) ◽  
pp. 431-447 ◽  
Author(s):  
B Scubon-Mulieri ◽  
R L Parsons
Keyword(s):  
Neuromuscular Junction ◽  
Intracellular Calcium ◽  
Time Constant ◽  
Time Course ◽  
Frog Neuromuscular Junction ◽  
Rate Of Development ◽  
Recovery Interval ◽  
Cyclic Model ◽  
Input Conductance ◽  
External Calcium

The time course of carbachol-induced desensitization onset and recovery of sensitivity after desenitization have been compared at the frog neuromuscular junction. The activation-desensitization sequence was determined from input conductance measurements using potassium-depolarized muscle preparations. Both desensitization onset and recovery from desensitization could be adequately described by single time constant expressions, with tauonset being considerably shorter than taurecovery. In nine experiments, tauonset was 13+/-1.3 s and taurecovery was 424+/-51 s with 1 mM carbachol. Elevating the external calcium or carbachol concentration accelerated desensitization onset without changing the recovery of sensitivity after equilibrium desensitization. Desensitization onset was accelerated by a prior activation-desensitization sequence to an extent determined by the recovery interval that followed the initial carbachol application. The time course of return of tauonset was closely parallel to, but slower than the time course of recovery of sensitivity. These results are consistent with a cyclic model in which intracellular calcium is a factor controlling the rate of development of desensitization.

Time course of miniature end-plate currents at different sites on the frog neuromuscular junction

1988 ◽  
Vol 19 (6) ◽  
pp. 566-573
Author(s):  
E. G. Bezgina ◽  
T. M. Drabkina ◽  
S. N. Zemskova ◽  
A. L. Zefirov ◽  
L. A. Kashapova ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Time Course ◽  
Frog Neuromuscular Junction ◽  
End Plate

scholarly journals Equilibrium Potential for the Postsynaptic Response in the Squid Giant Synapse

1974 ◽  
Vol 64 (5) ◽  
pp. 519-535 ◽  
Author(s):  
R. Llinás ◽  
R. W. Joyner ◽  
C. Nicholson
Keyword(s):  
Time Course ◽  
Reversal Potential ◽  
Input Resistance ◽  
Equilibrium Potential ◽  
Minimal Amount ◽  
Synaptic Potential ◽  
Synaptic Current ◽  
Isolated Segment ◽  
Squid Giant Synapse ◽  
Giant Synapse

The reversal potential for the EPSP in the squid giant synapse has been studied by means of an intracellular, double oil gap technique. This method allows the electrical isolation of a portion of the axon from the rest of the fiber and generates a quasi-isopotential segment. In order to make the input resistance of this nerve segment as constant as possible, the electroresponsive properties of the nerve membrane were blocked by intracellular injection of tetraethylammonium (TEA) and local extracellular application of tetrodotoxin (TTX). Thus, EPSP's could be evoked in the isolated segment with a minimal amount of electroresponsive properties. The reversal potential for the EPSP (EEPSP) was measured by recording the synaptic potential or the synaptic current during voltage clamping. The results indicate that EEPSP may vary from +15 to +25 mV, which is more positive than would be expected for a 1:1 conductance change for Na+ and K+ (approximately -15 mV) and too negative for a pure Na+ conductance (+40 mV). This latter value (ENa) was directly determined in the voltage clamp experiments. The results suggest that the synaptic potential is probably produced by a permeability change to Na+ to K+ in a 4:1 ratio. No change in time-course was observed in the synaptic current at clamp levels of -100 and +90 mV. The implications of a variable ratio for Na+-K+ permeability in subsynaptic-postsynaptic membranes are discussed.

Time course and magnitude of effects of changes in tonicity on acetylcholine release at frog neuromuscular junction

1977 ◽  
Vol 40 (2) ◽  
pp. 212-224 ◽  
Author(s):  
H. Kita ◽  
W. van der Kloot
Keyword(s):  
Neuromuscular Junction ◽  
Time Course ◽  
Control Level ◽  
Synaptic Function ◽  
Hypertonic Solution ◽  
Frog Neuromuscular Junction ◽  
Surface Charges ◽  
Hypertonic Solutions ◽  
After Hours ◽  
Reported Data

1. The time course for the changes in miniature end-plate potential (min epp) frequency and in epp amplitude produced by alterations in the tonicity of the Ringer at the frog neuromuscular junction was studied. The relations between the tonicity and min epp frequency as well as epp amplitude were also investigated. 2. The change in min epp frequency occurred within 1 min after the start of the change in the tonicity of the extracellular solution. Following a shift to a hypertonic solution, the min epp frequencies were often maintained at a relatively steady, elevated level, even with large (+100 mosM) changes in tonicity. In other instances the elevation was transitory like the reported data for the rat neuromuscular junction. Essentially the same results were obtained in very low Ca2+-Ringer. Unlike the rat neuromuscular junction, the final level after hours of the increased min epp frequency caused by raising the osmolarity by more than 75 mosM was well above the control level. Following the return from a hypertonic to an initial solution there was a prompt decrease in min epp frequency to about the initial level; there was no indication of the transitory depression in min epp frequency following the return from hypertonic solution that has been reported in mammals. 3. Until the osmolarity of the Ringer reached about 420 mosM, the frequency of min epp continued to rise along a line relating log (min epp frequency) to (osmolarity)0.5. When the osmolarity exceeded 460 mosM, the relation started to level off. 4. The hypothesis that the min epp frequency in a Ringer with a given increased tonicity is a fixed multiple of the frequency in normal Ringer is not in accord with the data. 5. The decrease in epp amplitude caused by markedly hypertonic solutions also came about within 1 or 2 min after the start of the change in the tonicity of the solution surrounding the nerve terminal. 6. Hypertonic solutions did not appear to affect facilitation. 7. Below 360 mosM increasing the tonicity of the Ringer had little effect on the amplitude of epp. Above this level the amplitude decreased as the tonicity increased. At a given junction an increase in tonicity in a range above 360 mosM can cause an increase in min epp frequency and a decrease in epp amplitude. 8. The results are discussed in terms of the theories proposed to account for the effects of osmolarity on synaptic function. Two theories--the water flow hypothesis (11) and the barrier of water hypothesis (2)--do not fit with the results. The two other theories--calcium elevation (1) and screening of surface charges (3, 13, 21)--fail to account for important aspects of the results and therfore cannot be accepted without substantial modifications. None of the theories devised to account for the increase in min epp frequency predicts the falloff in frequency and in evoked quantal release that occurs in highly hypertonic solutions.

Differences in presynaptic action of 4-aminopyridine and tetraethylammonium at frog neuromuscular junction

1987 ◽  
Vol 65 (5) ◽  
pp. 747-752 ◽  
Author(s):  
M. I. Glavinović
Keyword(s):  
Neuromuscular Junction ◽  
Transmitter Release ◽  
Action Potentials ◽  
Time Course ◽  
Potassium Conductance ◽  
Frog Neuromuscular Junction ◽  
Quantal Content ◽  
Low Concentrations ◽  
Voltage Dependent ◽  
Intracellular Ca

4-Aminopyridine markedly potentiates transmitter release at the frog cutaneous pectoris neuromuscular junction by increasing the quantal content even when applied at low concentrations (5–20 μM). This enhancement of transmitter release is associated with greater minimum synaptic latency, but the dispersion of the synaptic latencies does not appear much affected. This is in contrast with the action of tetraethylammonium (0.2–0.5 mM) in which case similar enhancement of transmitter release results not only in larger minimum synaptic latency but also in greater dispersion of the synaptic latencies. The time course of transmitter release associated with enhanced transmitter output is hence much more prolonged in the presence of tetraethylammonium than 4-aminopyridine, at least for low concentrations of 4-aminopyridine (5–20 μM). This indicates that their presynaptic actions differ significantly. This conclusion is further strengthened by the finding that unlike tetraethylammonium, 4-aminopyridine induces bursts of release, presumably by producing multiple action potentials in the nerve terminal. Tetraethylammonium probably acts by blocking the delayed potassium conductance, but the blockade of Ca2+-activated K+ conductance cannot be excluded. 4-Aminopyridine, however, probably blocks the fast inactivating (IA) K+ current, but it also may be acting directly on the voltage-dependent Ca2+ conductance or on the intracellular Ca2+ buffering.

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